Previous investigations have established that carcinogenic polyclic aromatic hydrocarbons, such as benzo(a)pyrene (BP), are rapidly metabolized by human fetal and guinea pig adrenal glands. Since in some tissues, BP is converted to highly reactive metabolites by cytochrome P-450-dependent enzymes, studies will be carried out to characterize the products of adrenal BP metabolism and to examine the factors affecting adrenal BP hydroxylase activity. Using the guinea pig as the experimental animal, adrenal conversion of BP to "activated" metabolites that covalently bind to cellular macromolecules (DNA, RNA, protein) will be evaluated and compared with hepatic "activation". Effects of epoxide hydrase and/or BP hydroxylase inhibitors on the formation of macromolecular-binding metabolites will be assessed simultaneously. The identity of BP metabolites produced by adrenal tissue will be determined using high-pressure liquid chromatography (HPLC) and compared with those produced by hepatic microsomes. In related studies, the effects on BP metabolism and the formation of "active" metabolites of various factors (age, sex, ACTH, androgens) known to influence adrenal mixed function oxidases, will be investigated. In addition, using human adrenals obtained from breast carcinoma patients, we will determine if adult adrenal tissue, like that in the human fetus, metabolizes BP. If so, we will also determine if DNA, RNA or protein-binding metabolites are formed and, using HPLC, attempt to identify BP metabolites produced by human adrenal tissue.